KR20120039121A - Composition for recovering muscle fatigue or enhancing muscle comprising nadh and method thereof - Google Patents

Abstract

PURPOSE: A composition containing NADH is provided to quickly recover muscle fatigue by NADH. CONSTITUTION: A pharmaceutical composition for recovering muscle fatigue contains NADH(nicotinamide adenine dinucleotide) as an active ingredient. The muscle is red muscle. The effective amount of NADH is 1-20 mM. The composition is used in the form of a tablet, pill, capsule, granule, powder, liquid, or injection solution. A health food composition for preventing muscle fatigue contains NADH as an active ingredient. The health food composition is a solid food, gel phase food or drink.

Description

COMPOSITION FOR RECOVERING MUSCLE FATIGUE OR ENHANCING MUSCLE COMPRISING NADH AND METHOD THEREOF}

The present invention relates to a composition for restoring and / or strengthening muscle fatigue using NADH as an active ingredient and a method for recovering the same.

In general, when severe exercise, glycogen-derived glucose in muscle is used, and anoxic glycolysis proceeds to synthesize ATP necessary for muscle contraction. In addition, the lactic acid, which is a metabolite, accumulates, and the intramuscular pH decreases, thereby reducing the efficiency of muscle contraction.

This state is called metabolic asisosis and as a result, it is thought that it leads to muscle fatigue. Therefore, it is important not to cause metabolic asissis in order to suppress muscle fatigue caused by continuous exercise.

In such a method of restoring muscle fatigue, fatigue may be improved through administration of a drug or supplement. In the case of drug administration, it is complicated because diagnosis or prescription response by a doctor or the like is required. On the other hand, the countermeasure by diet as a supplement is easy and easily absorbed into daily life, and in recent years, the research and development and product development are progressing, and the supplement market is expanding.

For example, intake of creatine as a supplement among sports athletes is prevalent. Creatine is converted into creatine phosphate in the body and has the effect of transporting energy as a high-energy phosphate compound.In addition, it is indispensable to ATP synthesis, and creatine intake increases muscle content of creatine and improves high-intensity exercise performance. Known (Harris, RC et al: Clin. Sci., 83, 367-374, 1992).

Leucine, isoleucine and valine are also called branched chain amino acids (BCAAs), and mixtures of these three types of amino acids are known to have muscle fatigue recovery effects (see, for example, JP-A-8-198748). Mixtures of these three types of BCAAs have been widely used as nutrients in the preparation of granules or drinks, but they are metabolized relatively quickly immediately after being absorbed into the small intestine, making them unsuitable for sustained effects in restoring muscle fatigue.

In addition, nutritional supplements containing whey protein, degradation products of whey protein or soy protein are known, but are known to have no lasting effect on muscle fatigue recovery (eg, Gastzoenferology, 7, 151-161 (1976) and Gut, 14, 494-501 (1974).

NADH is an abbreviation of Nicotinamide adenine dinucleotide reduced form, which is a reduced form of NAD and a reduced coenzyme of vitamin B3, which is rich in electrons, that is, energy. These NADHs are important electron donors in vivo, which not only interconvert each other in numerous metabolic activities but also act as coenzymes of various enzymes in the body. In other words, this coenzyme exists in the oxidized form of NAD ⁺ and the reduced form of NADH in the cell, and NAD receives electrons from other molecules as oxidant and becomes NADH in reduced form, and NADH plays a role of giving electron as reducing agent.

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems and the above-mentioned necessity, and an object of the present invention is to provide an effective muscle fatigue recovery agent.

Another object of the present invention is to provide an effective muscle fatigue recovery method.

Another object of the present invention is to provide an effective muscle strengthening composition and a method of strengthening the same.

In order to achieve the above object, the present invention provides a pharmaceutical composition for muscle fatigue recovery, comprising nicotinamide adenine dinucleotide reduced form (NADH) as an active ingredient.

In a preferred embodiment of the present invention, the muscle is preferably red muscle, but is not limited thereto.

In one embodiment of the invention, the effective amount of the NADH is preferably 1 ~ 20mM, but is not limited thereto.

In a preferred embodiment of the present invention, the composition is preferably used in the form of tablets, pills, capsules, granules, powders, powders, solutions or injections, but is not limited thereto.

In another aspect, the present invention provides a nicotine amide adenine dinucleotide reduced form (NADH) as an active ingredient, provides a health food composition for preventing and improving muscle fatigue.

In one embodiment of the present invention, the health food is preferably a solid food, gel food or beverage, but is not limited thereto.

The present invention also provides a method for restoring muscle fatigue, comprising administering nicotinamide adenine dinucleotide urea reduced form (NADH) to a human.

In another aspect, the present invention provides a method for preventing and improving muscle fatigue, comprising administering to a human a health food comprising nicotinamide adenine dinucleotide urea reduced form (NADH).

Hereinafter, the present invention will be described.

The composition for muscle fatigue recovery of the present invention may be a composition for any use for improving exercise physiological function, for example, food, health food, functional food, pharmaceutical composition and the like. In any use, the composition can be appropriately prepared by a method known in the form of solids or solutions such as tablets, pills, capsules, granules, powders, powders, liquids and the like. That is, the solid preparation or liquid preparation useful as the muscle fatigue recovery agent of the present invention is prepared by mixing NADH with various additives as necessary, and using a well-known preparation method well established in the prior art. For example, excipients, pH adjusters, fresheners, suspending agents, diluents, defoamers, viscous agents, dissolution aids, disintegrants, binders, lubricants, antioxidants, coatings, colorants, surfactants, plasticizers, sweeteners or flavorings, etc. What is necessary is just to use as said composition.

Examples of the excipient include sugar alcohols such as D-sorbet, D-mannitol or xylitol, sugars such as glucose, white sugar, lactose or fructose, crystalline cellulose, sodium carmellose, calcium hydrogen phosphate, wheat starch and rice starch. , Corn starch, potato starch, dextrin, cyclodextrin, hard silicic anhydride, titanium oxide, magnesium metasilicate or the like.

As said pH adjuster, citric acid, malic acid, sodium hydrogen phosphate, a potassium diphosphate, etc. are mentioned, for example.

As said refreshing agent, 1-menthol, mint water, etc. are mentioned, for example.

As the suspending agent, for example, kaolin, caramelose sodium, xanthan gum, methyl cellulose or tragant and the like can be mentioned.

As said diluent, purified water, ethanol, vegetable oil, an emulsifier, etc. are mentioned, for example.

Examples of the defoamer include dimethylpolysiloxane, silicone defoamer, and the like.

Examples of the viscous agent include xanthan gum, tragant, methyl cellulose or dextrin.

As said dissolution adjuvant, ethanol, sucrose fatty acid ester, macrogol, etc. are mentioned, for example.

Examples of the disintegrating agent include low-substituted hydroxypropyl cellulose, carboxymethyl cellulose calcium, croscarmellose sodium, hydroxypropyl starch or partially alpha starch.

As said binder, for example, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethyl cellulose, polyvinyl alcohol, pullulan, alpha starch, agar, tragant And sodium alginate or propylene glycol esters.

Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hardened oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax or pewter (White beeswax). .

Examples of the antioxidant include dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, ascorbic acid or citric acid.

As the coating agent, for example, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate, Polyvinyl acetal diethyl amino acetate, amino alkyl methacrylate copolymer, hydroxypropyl methyl cellulose acetate succinate, methacrylic acid copolymer, polyvinylacetate diethyl amino acetate, shellac and the like.

As said coloring agent, a turmeric extract, riboflavin, a titanium oxide, a carotene liquid, etc. are mentioned, for example.

As the sweetener, for example, fructose, D-sorbet, glucose, sodium saccharin, sweet syrup, white sugar, honey, flax tea, licorice, citric acid, adipic acid, ascorbic acid, orange oil, dough heat (Orange peel) tincture), fennel oil, peppermint or mentle.

As said surfactant, For example, polyoxyethylene hardened castor oil, glycerol monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, And macrogols or sucrose fatty acid esters.

As said plasticizer, triethyl citrate, polyethyleneglycol, triacetin, cetanol, etc. are mentioned, for example.

As said fragrance | flavor, natural fragrances, such as an animal fragrance or a vegetable fragrance | flavor, or synthetic fragrances, such as an isolated fragrance or a synthetic fragrance | flavor, etc. are mentioned, for example.

The amount of NADH in the formulation is usually about 1 to 80% by weight, preferably about 2 to 40% by weight, based on the entire formulation.

In the case of food, it is manufactured by mix | blending NADH or the said NADH containing agent at the time of food preparation.

For example, solid foods such as bread, chewing gum, cookies, chocolate, cereals, jams such as jams, ice cream, yogurt, jelly, cream or gel foods, juice, coffee, cocoa, green tea, oolong tea, black tea, etc. It can be in any food form such as a drink. Moreover, it can also mix | blend with seasoning, food additive, etc.

The composition for restoring muscle fatigue of the present invention varies depending on the kind, its dosage form, and also the age, weight, adaptation symptom or condition of the patient or intake patient, but, for example, in the case of oral medicine, several times a day for an adult ~ 500mg, preferably 3 ~ 200mg is good to administer. Moreover, even when it is ingested as a health food, there is no problem of side effects, and it is not a problem even if it ingests the same quantity as an oral medicine. The intake timing is not particularly set, but a higher effect can be expected by ingesting in particular between 1 hour before and after exercise.

Hereinafter, the present invention will be described in detail.

There is oxidative phosphorylation proteins (OXPHOS) in the plasma membrane of muscle cells. Supplying NADH to the outside of muscle cells causes cell respiration by myoplasmic membrane OXPHOS, protons move into muscle cells during the NADH-dependent myoplasmic membrane cell respiration, which causes acidification inside the muscle cells and increases the contractility of acidified muscle cells. In addition, recovery of muscle fatigue occurs quickly.

 Therefore, when NADH is supplied to the outside of the muscle cells, protons enter the cells through the OXPHOS of the muscle plasma membrane, and the pH inside the muscle cells decreases, so that the recovery of muscle fatigue can occur quickly.

In the present invention, the degree of muscle contraction after soleus and intestinal extensor muscle (EDL; extensor digitorum longus, for reference, is red muscle and EDL is white muscle) was examined.

As shown in FIG. 1, as the tetanus progresses, the contraction of the muscle drops sharply, but after a certain time, the contraction of the muscle recovers by about 48% (see FIGS. 1A-C).

Compared to the control group, the degree of muscle contraction caused by contraction after the injection of NADH into the soles of mice in the experimental group (NADH) was very similar to that of the control group, but the recovery of muscle contraction increased by 69% after a certain time (FIG. 2).

However, in the case of white muscle EDL, reduction and recovery of muscle contraction after contraction were not affected by NADH (FIG. 1).

As can be seen through the present invention, the supply of NADH to the red muscle has an effect that the recovery of muscle fatigue proceeds quickly.

Figure 1a shows the degree of contraction of white muscle EDL in the absence of NADH. This is a graph measuring muscle contraction after 0, 50, and 1400 seconds after stimulation.
1B shows the degree of contraction of white muscle EDL in the presence of 5 mM NADH. This is a graph measuring muscle contraction after 0, 50, and 1400 seconds after stimulation. The vertical axis represents force as shown in FIG. 1A.
Figure 2a shows the degree of contraction of the red muscle soleus muscle in the absence of NADH. It is a graph showing muscle contraction after 0, 100, 1300 seconds after the contraction stimulation.
2B shows the degree of contraction of the red muscle soles in the presence of 5 mM NADH. This graph shows muscle contraction after 0, 100, 1300 seconds after the stimulus. The vertical axis represents force as shown in FIG. 2A.
Figure 2c shows the relative tension of the soleus in the absence of NADH and in the state of NADH injected. After tension stimulation, muscle tone was examined for various times.
Figure 3 is a graph showing the relative degree of contraction by the NADH of the white muscle extensor extensor extensor (EDL) in the fatigue and recovery conditions. In FIG. 3, Pi means a tetanic force peak of initiation state.
Figure 4 is a graph showing the relative degree of contraction by the NADH of red muscle soleus muscle (Soleus) in the fatigue and recovery conditions. In FIG. 4, Pi means a tetanic force peak of initiation state.

The present invention will now be described in more detail by way of non-limiting examples. The following examples are intended to illustrate the invention and the scope of the invention is not to be construed as being limited by the following examples.

NADH used in the present invention was purchased from Calbiochem.

Comparative example : White muscle Intestinal extensor (EDL) Nicotinamide  Adenine Dainew Creo Thai Fatigue and Fatigue Recovery Test by Reduction Type

The composition of the experimental animals and solutions used in the experiment of the present invention is as follows.

Experiment animal C57BL / 6 7week male mouse

Solution mouse Krabs-Henseleit solution (118 mM NaCl, 4.75 mM KCl, 2.54 mM CaCl ₂ , 1.18 MgSO ₄ , 1.18 mM NaH ₂ PO ₄ , 24.8 mM NaHCO ₃ , 10 mM Glucose, pH 7.4)

Experimental method of the present invention was carried out as follows.

After anesthesia with IV (abdominal injection) of sodium pentobarbital (50 mg / kg), the muscles were quickly removed using a surgical silk thread and tied to the ligaments and tendons at both ends and placed in a 5 ml bath containing gastric solution for 5 minutes. Adapted. The solution was supplied with constant oxygen at 95% / 5% oxygen / carbon dioxide gas. Bath temperature was maintained at 37 ° C. through a TC-10 temperature controller (Corner stone US). In the tank, platinum electrodes were installed on both sides of the muscle. Stimulation was performed using DMC (dynamic muscle control, Solwood Enterprise, Inc.) software, Grass S48 Stimulator (Grass instrument, Quincy, mass, USA), Dual-mode lever arm system (Aurora scientific, inc., Ontario, Canada) To control. The device can control the stimulation time, frequency, and voltage of the muscles. Muscle contraction exercises were quantified of force through Dynamic Muscle Analysis, Solwood Enterprise, Inc. (DMA).

Optimal muscle length and optimal stimulate conditions were achieved by twitches contraction before muscle fatigue experiments.

Muscle fatigue experiments were performed under the following conditions.

Stimulation conditions: bowel extensor (500 ms duration, 140 pps, frequency, 100 V voltage)

  Muscle immersed in 5ml K-H solution control and 5mM NADH / 5ml K-H solution induced 50 fatigue contractions for 50 seconds each to give muscle fatigue. After muscle fatigue stimulation, the solution in the bath was replaced by 5 ml each and had a recovery phase of 10 minutes (600 seconds). After 10 minutes of recovery time, strength was measured with one stretch. Afterwards, strength data was obtained through additional stretching.

The results of the experiment are shown in FIG. 3.

As can be seen in Fig. 3, the fatigue state is induced through continuous stimulation under conditions of 500 ms duration, 140 pps, frequency, 100 V voltage up to 50 seconds, during which the force is measured with axle, and then over 10 minutes. After the recovery time, strength was measured with a single axle. In addition, after another 10 minutes of recovery time, strength was measured with one stretch. As can be seen in Figure 3, it can be seen that muscle fatigue relief and fatigue recovery rate by NADH does not increase.

Example  : Red muscle  Soleus ( Soleus )of Nicotinamide  Adenine Dainew Creo Fatigue due to tide reduction type and Recovery  Measurement experiment

The composition of the experimental animals and solutions used in the experiment of the present invention is as follows.

Laboratory animals; C57BL / 6 7week male mouse

solution; mouse Krabs-Henseleit solution (118 mM NaCl, 4.75 mM KCl, 2.54 mM CaCl ₂ , 1.18 MgSO ₄ , 1.18 mM NaH ₂ PO ₄ , 24.8 mM NaHCO ₃ , 10 mM Glucose, pH 7.4)

Experimental method was carried out as follows.

After anesthesia with IV (abdominal injection) of sodium pentobarbital (50 mg / kg), the muscles were quickly removed using a surgical silk thread and tied to the ligaments and tendons at both ends and placed in a 5 ml bath containing gastric solution for 5 minutes. Adapted. The solution was supplied with constant oxygen at 95% / 5% oxygen / carbon dioxide gas. Bath temperature was maintained at 37 ° C. through a TC-10 temperature controller (Corner stone US). In the tank, platinum electrodes were installed on both sides of the muscle. Stimulation was performed using DMC (dynamic muscle control, Solwood Enterprise, Inc.) software, Grass S48 Stimulator (Grass instrument, Quincy, mass, USA), Dual-mode lever arm system (Aurora scientific, inc., Ontario, Canada) To control. The device can control the stimulation time, frequency, and voltage of the muscles. Muscle contraction exercises were quantified of force through Dynamic Muscle Analysis, Solwood Enterprise, Inc. (DMA).

Optimal muscle length and optimal stimulate conditions were achieved by twitches contraction before muscle fatigue experiments.

Muscle fatigue experiments were performed under the following conditions.

  Stimulation conditions: soleus muscle (1000 ms duration, 200 pps frequency, 100 V voltage)

Muscles immersed in 5ml K-H solution control and 5mM NADH / 5ml K-H solution induced 100 fatigue contractions for 50 seconds each to give muscle fatigue. After muscle fatigue stimulation, the solution in the bath was replaced by 5 ml each and had a recovery phase of 10 minutes (600 seconds). After 10 minutes of recovery time, strength was measured with one stretch. Afterwards, strength data was obtained through additional stretching.

The results of the experiment are shown in FIG. 4.

As can be seen in Figure 4, under the conditions of 1000 ms duration, 200 pps frequency, 100 V voltage up to 50 seconds, the fatigue state is induced through the continuous stimulation, while the force is measured in the axis, and then recovered over 10 minutes After a period of time, strength was measured with a single axle. In addition, after another 10 minutes of recovery time, strength was measured with one stretch. As shown in Figure 4, it can be seen that muscle fatigue relief and fatigue recovery rate by NADH was increased.

Therefore, the comparative examples and examples are examples related to fatigue reduction and increased fatigue recovery by nicotinamide adenine dinucleotide urea reduced form (NADH). Based on these results, fatigue and fatigue recovery were not affected by nicotine amide adenine dinucleotide reduced form (NADH) in white muscle, but fatigue by nicotine amide adenine dyneucretide reduced form (NADH) in red muscle. An increase in alleviation and fatigue recovery was observed. This fact can be expected to alleviate fatigue and increase fatigue recovery by increasing the concentration of nicotinamide adenine dinucleotide urea reduced (NADH) in the human body in the future. In particular, it is expected to contribute to the relaxation of fatigue and the speed of fatigue recovery of sports athletes and physical workers who use the human body a lot.

Claims (12)

A pharmaceutical composition for restoring muscle fatigue, comprising nicotinamide adenine dinucleotide reduced form (NADH) as an active ingredient. According to claim 1, wherein the muscle is muscle fatigue recovery pharmaceutical composition, characterized in that the red muscle. The pharmaceutical composition for restoring muscle fatigue according to claim 1, wherein the effective amount of NADH is 1-20 mM. The pharmaceutical composition for restoring muscle fatigue according to claim 1, wherein the composition is used in the form of tablets, pills, capsules, granules, powders, powders, solutions or injections. A healthy food composition for preventing and improving muscle fatigue, comprising nicotine amide adenine dinucleotide reduced form (NADH) as an active ingredient. The method of claim 5, wherein the muscle is a red muscle, characterized in that the muscle fatigue prevention and improvement health food composition. 6. The healthy food composition for preventing and improving muscle fatigue according to claim 5, wherein the health food is a solid food, a gel food or a beverage. A method of restoring muscle fatigue comprising administering nicotinamide adenine dynucretide reduced form (NADH) to a human. A method for preventing and improving muscle fatigue, comprising administering to a human a health food comprising nicotine amide adenine dinucleotid reduced form (NADH). A composition for strengthening muscles, comprising nicotinamide adenine dinucleotide urea reduction type (NADH) as an active ingredient. 11. The muscle strengthening composition of claim 10, wherein the muscle is a red muscle. A method of strengthening muscles comprising administering nicotinamide adenine dynucretide reduced form (NADH) to a human.

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